TyG-BMI and risk of CKD progression: Mediation by oxidative stress, fibrosis, and metabolic dysfunction

To investigate the association between the triglyceride-glucose-body mass index (TyG-BMI) and chronic kidney disease (CKD) progression in individuals across the cardiovascular-kidney-metabolic spectrum, and to evaluate the potential mediation by biomarkers of oxidative stress, inflammation, and fibrosis. This study included 9265 adults stratified into cardiovascular-kidney-metabolic stages 0 to 4. Logistic regression and restricted cubic splines assessed the relationship between TyG-BMI and CKD progression. Mediation analysis quantified the indirect effects of the uric acid-to-high-density lipoprotein ratio, fibrosis-4 index, and red cell distribution width-to-albumin ratio. The primary finding of this study is that elevated TyG-BMI significantly increases the risk of chronic kidney disease (CKD) progression. Specifically, for each unit increase in TyG-BMI, the risk of CKD progression rose by 16% (OR = 1.16; 95% CI:1.01-1.30). This association was quantitatively and significantly mediated by the uric acid-to-high-density lipoprotein ratio, the fibrosis-4 index, and the red cell distribution width-to-albumin ratio, indicating the involvement of oxidative, fibrotic, and inflammatory pathways. Our analysis suggests that elevated TyG-BMI may be associated with an increased risk of CKD progression, potentially mediated through oxidative, inflammatory, and fibrotic pathways. These findings warrant further investigation to confirm the potential clinical relevance of TyG-BMI and the implicated pathways.